2019年12月
13-(2-Methylbenzyl) Berberine Is a More Potent Inhibitor of MexXY-Dependent Aminoglycoside Resistance than Berberine
ANTIBIOTICS-BASEL
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- 巻
- 8
- 号
- 4
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.3390/antibiotics8040212
- 出版者・発行元
- MDPI
We previously showed that berberine attenuates MexXY efflux-dependent aminoglycoside resistance in Pseudomonas aeruginosa. Here, we aimed to synthesize berberine derivatives with higher MexXY inhibitory activities. We synthesized 11 berberine derivatives, of which 13-(2-methylbenzyl) berberine (13-o-MBB) but not its regiomers showed the most promising MexXY inhibitory activity. 13-o-MBB reduced the minimum inhibitory concentrations (MICs) of various aminoglycosides 4- to 128 fold for a highly multidrug resistant P. aeruginosa strain. Moreover, 13-o-MBB significantly reduced the MICs of gentamicin and amikacin in Achromobacter xylosoxidans and Burkholderia cepacia. The fractional inhibitory concentration indices indicated that 13-o-MBB acted synergistically with aminoglycosides in only MexXY-positive P. aeruginosa strains. Time-kill curves showed that 13-o-MBB or higher concentrations of berberine increased the bactericidal activity of gentamicin by inhibiting MexXY in P. aeruginosa. Our findings indicate that 13-o-MBB inhibits MexXY-dependent aminoglycoside drug resistance more strongly than berberine and that 13-o-MBB is a useful inhibitor of aminoglycoside drug resistance due to MexXY.
- リンク情報
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- DOI
- https://doi.org/10.3390/antibiotics8040212
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/31698691
- PubMed Central
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6963850
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000506678800056&DestApp=WOS_CPL
- Scopus
- https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85074698903&origin=inward 本文へのリンクあり
- Scopus Citedby
- https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85074698903&origin=inward
- ID情報
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- DOI : 10.3390/antibiotics8040212
- eISSN : 2079-6382
- PubMed ID : 31698691
- PubMed Central 記事ID : PMC6963850
- SCOPUS ID : 85074698903
- Web of Science ID : WOS:000506678800056